Aspirin might have antioxidant properties and plays an important role in inflammation. Promising evidence from the in vitro fertilization (IVF) literature suggests that low-dose aspirin may improve fecundity, possibly due to improved perfusion early in pregnancy. We conducted a meta-analysis of randomized IVF clinical trials that suggested that aspirin during early gestation may reduce the risk of preterm birth and small-for-gestational-age babies. The EAGeR study will be a multi-site, double-blinded randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcome. It will be the largest such study to-date, enrolling 1,600 women experiencing a recent pregnancy loss who are planning subsequent pregnancies. Each woman will be randomly assigned to the treatment group with 81 mg aspirin plus 0.4 mg folic acid daily or the placebo group with 0.4 mg folic acid only. Treatment/placebo administration will start prior to conception and continue during pregnancy. Fertility monitors will be used to assist with timing of intercourse, home digital pregnancy testing kits will be used to determine pregnancy, and daily urine samples will be collected to monitor very early pregnancy and pregnancy loss. Pregnancy loss, pregnancy complications and perinatal outcomes will be monitored throughout pregnancy. We hypothesize that low-dose aspirin may reduce oxidative stress and inflammation and, therefore, reduce vascular resistance and improve blood flow and placental perfusion. An increased supply of oxygen and nutrients should promote placental and fetal growth, enhance conception rates, reduce pregnancy loss and pregnancy complications and, thereby, improve perinatal outcomes. Findings from this trial will have important implications not only for women trying to conceive but also for women who want to maintain a healthy pregnancy and achieve optimal perinatal outcomes. We will utilize the methods we have developed related to pooling in certain sub-studies, such as the study of compliance with assigned treatment.